Substituted 2-phenylimidazo[4,5-c]pyridines are known. The compounds are useful as inotropic agents, anticoagulants, bronchodilators, and vasodilators. One especially useful class of 2-phenylimidazo[4,5-c]pyridines are those in which the phenyl moiety is substituted with an alkylsulfinyl group.
Such compounds generally are prepared by cyclizing an N-(3-amino-4-pyridinyl)alkylthiobenzamide to an alkylthio substituted phenylimidazo[4,5-c]pyridine. This cyclization step often occurs under extreme conditions, such as refluxing POCl.sub.3, or POCl.sub.3 in pyridine. After cyclization, the alkylthio group is oxidized to the required alkylsulfinyl moiety using entirely different reaction conditions.
European Patent Application No. 93,593 is representative of the typical two step process used to produce such compounds. The reference describes reacting a 3,4-diamino pyridine with an alkylthio substituted benzoic acid or benzoic acid derivative to form an alkylthio substituted 2-phenylimidazo[4,5-c]pyridine, followed by oxidation of the alkylthio group to an alkylsulfinyl group. The cyclization reaction is preferably conducted in dehydrating agents such as polyphosphoric acid or phosphorus oxychloride, while the oxidation reaction requires an oxidizing agent such as m-chloroperbenzoic acid, t-butylhypochlorite, or hydrogen peroxide.
The prior art fails to suggest the use of an oxidizing agent in an alkanoic acid to effect cyclization and oxidation of N-(3-amino-4-pyridinyl)alkylthiobenzamides to alkylsulfinyl 2-phenylimidazo[4,5-c]pyridines. The present invention provides a process which employs an oxidizing agent in an alkanoic acid to perform both the cyclization and oxidation steps. The invention thus obviates the need to isolate intermediates, since both steps employ the same reaction conditions. In addition, the cyclization portion of the present process is more facile than previously disclosed cyclization reactions, thus allowing the process to be conducted under milder reaction conditions.